Reversibility of ischemic findings on 3-T T2*-weighted imaging after emergency superficial temporal artery-middle cerebral artery anastomosis in patients with progressive ischemic stroke.

Vascular ischemic signs, i.e. multiple hypointense vessels in the ischemic territory, were identified by gradient echo-type 3-T T(2)*-weighted magnetic resonance (MR) imaging in 3 patients with acute ischemia due to major vessel occlusion. Emergency superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis was performed in 2 patients with progressive stroke caused by bleeding-type moyamoya disease or severe MCA stenosis. Both patients were initially treated conservatively, but their neurological signs deteriorated. 3-T T(2)*-weighted MR imaging detected funicular low signals in both patients indicating enhancement of cortical vessels or medullary veins. The area of the vascular ischemic signs was almost the same or smaller than the hypoperfusion area on perfusion-weighted MR imaging or single-photon emission computed tomography. Postoperatively, the vascular ischemic signs disappeared in both patients, suggesting a relationship with severe ischemia due to high-risk misery perfusion. Their postoperative course was uneventful, and MR imaging revealed no new cerebral ischemic lesions or cerebral hyperperfusion. The patient without surgery developed cerebral infarction in the area of the vascular ischemic signs. Vascular ischemic signs detected by 3-T T(2)*-weighted MR imaging may represent a new predictor of high-risk misery perfusion, and may disappear after STA-MCA anastomosis performed in the subacute stage.

Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients.

PURPOSE: Proinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-alpha) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients. METHODS: Thirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1beta, IL-6, IL-10, and TNF-alpha were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC). RESULTS: In the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02-1.54). CONCLUSION: In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.

Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized low-density lipoprotein and plaque vulnerability.

OBJECTIVE: Although carotid endarterectomy (CEA), the gold standard in stroke prevention, has been performed in the late stage after the insult, its optimal timing remains unclear. Using biomarkers in plaque and plasma, we evaluated oxidative stress and plaque vulnerability between early and late CEA in symptomatic patients. METHODS: We compared symptomatic stroke patients who underwent early CEA within 4 weeks of the last insult (group A; n = 15) with those who received CEA in the late stage beyond 4 weeks from the last symptom (group B; n = 57). They were divided into vulnerable (group Av, n = 13; group Bv, n = 33) and stable (group As, n = 2; group Bs, n = 24) subgroups according to the pathologic findings on their plaques. We studied the relationships among their primary symptoms, clinical findings, oxidized low-density lipoprotein levels, and gelatinase A (matrix metalloproteinase [MMP]-9) activity in their plaques and plasma. RESULTS: Group A had a variety of symptoms; there was no difference in the outcome of CEA between groups A and B. The plaque and plasma oxidized low-density lipoprotein levels were higher in group A than in group B (P < .05). The incidence of pathologically vulnerable plaque was higher in group A than in group B. Plaque oxidized low-density lipoprotein levels and MMP-9 activity were similar in group Av and group Bv and were higher in those groups than in group As and Bs. CONCLUSIONS: We first demonstrated that vulnerable plaques in patients subjected to early CEA manifested a remarkable increase in oxidized low-density lipoprotein and MMP-9 activation. Our findings suggest that early CEA may be beneficial in the aspect of oxidative stress.

Hemodynamic cerebral ischemia during carotid endarterectomy evaluated by intraoperative monitoring and post-operative diffusion-weighted imaging.

OBJECTIVE: We used the result of monitoring to evaluate patients with post-operative neurological deficits attributable to hemodynamic cerebral ischemia owing to cross-clamping of the carotid artery. METHODS: We evaluated 131 carotid endarterectomy (CEA) procedures performed on 118 patients, 96 men and 22 women ranging in age from 38 to 82 years (mean: 67.1 years). For monitoring, we used a combination of somatosensory evoked potential (SEP), functional dynamic electroencephalography (EEG), near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD). Patients who awoke with neurological deficits after CEA immediately underwent diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA). RESULTS: In 30 of the 131 procedures (22.9%), intraoperative monitoring disclosed abnormalities after cross-clamping of the internal carotid artery (ICA). In two of these 30 patients, shunt was not introduced, because of full recovery of monitoring after blood pressure increasing, however, one patient demonstrated transient ischemic attack (TIA). In six of remaining 28 patients who need shunt, transient hemodynamic cerebral ischemia occurred, however, all patients recovered gradually within 18 hours after CEA. No new lesions were detected on post-operative DWI of the seven patients and MRA demonstrated good patency of the carotid artery. The other 101 patients whose intraoperative monitoring after cross-clamping of the ICA did not disclose abnormalities demonstrated no hemodynamic TIA. CONCLUSION: Hemodynamic ischemia owing to cross-clamping of the ICA is rare in patients treated by CEA. However, in patients manifesting neurological deficits upon awakening from CEA, DWI and MRA should be performed immediately to facilitate their prompt treatment.

Hemichorea due to hemodynamic ischemia associated with extracranial carotid artery stenosis. Report of two cases.

In this paper the authors describe two patients with recurrent hemiparesis and limb shaking that gradually progressed to hemichorea. Cerebral angiography confirmed severe unilateral internal carotid artery stenosis (95%) contralateral to the hemichorea. The cerebral blood flow, assessed using N-isopropyl-p-(iodine-123) iodoamphetamine single-photon emission computed tomography (SPECT), disclosed markedly decreased vascular reserves in both patients. After carotid endarterectomy was performed, the hemichorea gradually subsided and SPECT confirmed increased cerebral perfusion. The results in these cases indicate that surgical revascularization is effective for hemichorea due to cerebral ischemia with reduced vascular reserve.

The use of continuous hemodiafiltration in a patient with diabetic ketoacidosis.

A variety of fatal complications are associated with diabetes mellitus. Among these, diabetic ketoacidosis (DKA) figures largely in fatalities in young diabetics. Although hyperosmotic diuresis in DKA causes extreme fluid loss, acute renal failure is less common than expected in DKA. We treated a case of severe DKA with associated coma, acute respiratory failure, and acute renal failure in a 24-year-old man who had been diagnosed with type 1 diabetes mellitus at age 19. The comatose patient had been intubated before transfer to our hospital for intensive care. Despite infusion with isotonic saline and insulin, metabolic acidosis was refractory. On day 2, urine output decreased and pulmonary congestion developed, so we started continuous veno-venous hemodiafiltration (CVVHDF), which was effective against the metabolic acidosis; urine output increased gradually. CVVHDF was withdrawn on day 7, and the patient's renal function recovered completely. He was discharged from the intensive care unit (ICU) on day 14.

Inhibition of brain damage by edaravone, a free radical scavenger, can be monitored by plasma biomarkers that detect oxidative and astrocyte damage in patients with acute cerebral infarction.

We assess the availability of plasma biomarkers to monitor the brain damage and the therapeutic efficacy of edaravone. The study consisted of 51 patients with ischemic cerebral infarcts. They were divided into 2 groups: GI (n = 24) had cortical lesions, and GII (n = 27) had lesions in the basal ganglia or brain stem. Edaravone was administered to 27 randomly selected patients (GIa, n = 13; GIIa, n = 14) and its efficacy was studied by comparing their plasma OxLDL, S-100B, and MnSOD levels to those in patients without edaravone (GIb, n = 11, GIIb, n = 13). Three days after the start of edaravone, plasma OxLDL was significantly lower in GIa than GIb patients (0.177 +/- 0.024 ng/microg apoB vs 0.219 +/- 0.026, P < 0.05). In GIIa patients, pre- and posttreatment plasma OxLDL was not significantly different (0.156 +/- 0.013 vs 0.152 +/- 0.020). In GIa patients, S-100B and MnSOD were significantly lower than in GIb patients (P < 0.05). The neurological condition at the time of discharge had recovered in GIa but not GIb patients. Ours is the first evidence to confirm the efficacy of edaravone by plasma biomarkers. In patients with cortical infarcts, edaravone reduced oxidative damage, thereby limiting the degree of brain damage.

Contribution of an imbalance between oxidant-antioxidant systems to plaque vulnerability in patients with carotid artery stenosis.

OBJECT: Reactive species of oxygen and nitrogen mediate the oxidative modification of low-density lipoprotein (LDL). Oxidation of LDL is inhibited by endogenous radical scavenging enzymes such as manganese superoxide dismutase (SOD) and Cu-ZnSOD that catalyze dismutation of oxygen to H2O2. Low-molecular antioxidants such as uric acid regulate the inactivation that appears to be linked to an increase in peroxynitrite resulting in oxidized LDL (OxLDL) elevation. The authors evaluated whether a focal imbalance between pro- and antioxidant systems induces plaque vulnerability in patients with carotid artery (CA) stenosis. METHODS: Carotid artery plaques obtained in 35 patients who had undergone carotid endarterectomy were classified as vulnerable or stable based on histopathological findings. In vulnerable plaques, OxLDL, measured using enzyme-linked immunosorbent assay, was significantly higher (p < 0.01) and SOD activity significantly lower than in stable plaques (p < 0.05). The plaque and plasma OxLDL levels were inversely correlated with plaque SOD activity (p < 0.01). The physiological uric acid level in all plaques was one fourth to one eighth of that in plasma and appeared to be unable to protect Cu-ZnSOD from degradation by H2O2. Immunohistochemical analysis showed increased peroxynitrite and OxLDL in vulnerable plaques. There was a significant correlation between plaque and plasma OxLDL levels (p < 0.01). CONCLUSIONS: Analysis of the results suggests that a focal imbalance between pro- and antioxidant defense systems in patients with CA plaques induces an increase in plaque OxLDL levels and consequent plaque instability, contributing to high levels of plasma OxLDL.

[Six cases of rhabdomyolysis induced by dehydration].

Rhabdomyolysis results from a variety of causes. We experienced 6 cases of rhabdomyolysis induced by dehydration in psychoneurosis patients or seniors. We should know dehydration as a risk factor for rhabdomyolysis especially in psychoneurosis patients or seniors.

Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement.

Oxidized low-density lipoprotein (OxLDL) plays a major role in atherosclerosis. We undertook the present study to clarify the relationship between plasma OxLDL and the ischemic volume. We used ELISA to determine plasma OxLDL levels, and performed diffusion- and perfusion-weighted MRI (DWI, PWI) to measure the ischemic volume in 44 ischemic stroke patients. Based on the location of the ischemic lesion, they were divided into three groups: Group I (GI, n = 21) had cortical lesions, Group II (GII, n = 17) had lesions in the basal ganglia or brain stem, and Group III (GIII, n = 6) had massive lesions that involved one entire hemisphere. In GI, but not GII and GIII, plasma OxLDL was significantly higher than in 19 age-matched controls (p < 0.01) and was significantly correlated with the initial ischemic volume visualized on DWI (p = 0.01), PWI (p < 0.01), and the DWI-PWI mismatch (p < 0.05). A persistent increase in plasma OxLDL was associated with enlargement of the ischemic lesion in the early phase after the insult. These findings suggest that elevated plasma OxLDL levels are associated with moderate ischemic damage in patients with cortical lesions (GI), but not those with massive hemispheric lesions (GIII), which may be irreversible. In addition, elevated plasma OxLDL may represent a predictor of enlargement of the ischemic lesion.

Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction.

Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.

Gene expression of D-amino acid oxidase in cultured rat astrocytes: regional and cell type specific expression.

Neuromodulative free D-serine is present in mammalian brain, and localized to type-2 astrocytes in culture. D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes D-amino acids. We examined the DAO gene expression in cultured rat astrocytes by reverse transcriptase-polymerase chain reaction. We established a method to prepare highly purified culture of type-1 and type-2 astrocytes from any brain region. This method utilizes combination of cell type specific separation by shaking and subsequent purification by immunopanning or treatment with cytosine arabinoside. We detected higher DAO gene expression in type-1 astrocyte cultures from cerebellum than that from cerebral cortex. In cerebellum, we observed higher DAO expression in type-1 astrocyte cultures than that in type-2. We also revealed that DAO expression in C6, corresponding to type-1 astrocyte, was higher than that in CG-4 derived type-2 astrocytes.